The objectives in this proposal are to elucidate the properties of I-region gene products on T-lymphocytes and to examine their relationship to T cell recognition and function. Although controversial, the presence of Ia determinants on thymus-derived lymphocytes has been suggested by many studies. Recently, we and others have overcome the difficulty in detecting these antigens using antisera produced in mice immunized with mitogen-stimulated T cell blasts. We propose to develop a variety of I-specific antibodies in this manner and to determine the extent of I subregion expression on the T cell surface. In addition we will establish whether Ia molecules are synthesized by the T cell and may be unique, or whether they are acquired from the surface of other cell types during immunocompetent cell interactions. We will confirm our finding of I-A region expression on T helper cells for B cell responses. Using antiserum plus complement treatment to deplete for Ia bearing cells, we will determine whether Ia is a marker for helper T cell differentiation and whether it defines a true functional heterogeneity among helper T cells. If so, this will be related to the functions of Ia positive T cells involved in the induction of cytotoxicity, delayed hypersensitivity, and suppression. Finally, experiments have been designed to test for the immunoregulatory role of T cell Ia. Does it contribute to the T cell receptor for antigen or does it function as an acceptor site for recognition by other T cells?